RESUMEN
Previous studies have shown the therapeutic properties of ginseng and ginsenosides on hyperactive and impulsive behaviors in several psychiatric diseases. Herein, we investigated the effect of Panax ginseng Meyer (PG) on hyperactive/impulsive behaviors in a manic-like animal model, sleep deprivation (SD) rats. Male rats were sleep-deprived for 48 h, and PG (200 mg/kg) was administered for 4 days, from 2 days prior to the start of SD to the end date of SD. The elevated plus maze (EPM) test showed that PG alleviated the increased frequency of entries into and spent time within open arms by SD. In order to investigate the molecular mechanism on this effect of PG, we assessed differentially expressed genes (DEGs) in the prefrontal cortex of PG-treated SD rats using RNA sequencing (RNA-seq) and performed gene-enrichment analysis for DEGs. The gene-enrichment analysis showed that PG most prominently affected the glutamatergic synapse pathway. Among the glutamatergic synapse pathway genes, particularly, PG enhanced the expressions of glutamate transporter Slc1a3 and Slc1a2 reduced in SD rats. Moreover, we found that PG could inhibit the SD-induced phosphorylation of the NR2A subunit of the NMDA receptor. These results suggested that PG might have a therapeutic effect against the manic-like behaviors, regulating the glutamatergic neurotransmission.
Asunto(s)
Antimaníacos/farmacología , Ginsenósidos/farmacología , Ácido Glutámico/metabolismo , Panax/química , Privación de Sueño/tratamiento farmacológico , Sueño REM/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Sistema de Transporte de Aminoácidos X-AG/metabolismo , Animales , Conducta Animal , Fármacos actuantes sobre Aminoácidos Excitadores/farmacología , Proteínas de Transporte de Glutamato en la Membrana Plasmática/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Privación de Sueño/metabolismo , Sinapsis/efectos de los fármacos , Sinapsis/metabolismoRESUMEN
Cancer-associated venous thromboembolism (CAT) is a common complication associated with high morbidity and mortality. In accordance with major clinical trials comparing low-molecular-weight heparin (LMWH) with a vitamin K antagonist (VKA), LMWH is currently the standard treatment for CAT, owing to its efficacy for thrombosis recurrence and improved safety profile compared to VKA. Over the past few years, direct oral anticoagulants (DOACs) have emerged as potential alternative therapies to LMWH due to their convenient route of administration and predictable pharmacokinetics, but evidence for their use in CAT is inconclusive, as only a small fraction of the study populations in these trials had CAT. Recently, two large head-to-head trials comparing DOACs to LMWH in CAT patients reported comparable efficacies of DOACs with increased bleeding risk. Occasionally, CAT treatment can be challenging due to the heterogeneity of underlying malignancies and comorbidities. Renal insufficiency and gastrointestinal defects are the main obstacles in anticoagulant selection. Careful choice of treatment candidates and proper anticoagulant strategies are critical for the treatment of CAT; hence, more studies are required to address these challenges.
Asunto(s)
Anticoagulantes/uso terapéutico , Neoplasias/patología , Tromboembolia Venosa/tratamiento farmacológico , Administración Oral , Ensayos Clínicos como Asunto , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Neoplasias/complicaciones , Insuficiencia Renal/complicaciones , Insuficiencia Renal/patología , Factores de Riesgo , Tromboembolia Venosa/etiología , Tromboembolia Venosa/patología , Vitamina K/antagonistas & inhibidoresRESUMEN
Cryptotanshinone (CTT) is a natural product and a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miltiorrhizabunge. Notably, CTT has a variety of anti-cancer actions, including the activation of apoptosis, anti-proliferation, and reduction in angiogenesis. We further investigated the anti-cancer effects of CTT using MTS, LDH, and Annexin V assay, DAPI staining, cell cycle arrest, and Western blot analysis in NSCLC cell lines. NSCLC cells treated with CTT reduced cell growth through PI3K/Akt/GSK3ß pathway inhibition, G0/G1 cell cycle arrest, and the activation of apoptosis. CTT induced an increase of caspase-3, caspase-9, poly-ADP-ribose polymerase (PARP), and Bax, as well as inhibition of Bcl-2, survivin, and cellular-inhibitor of apoptosis protein 1 and 2 (cIAP-1 and -2). It also induced G0/G1 phase cell cycle arrest by decreasing the expression of the cyclin A, cyclin D, cyclin E, Cdk 2, and Cdk 4. These results highlight anti-proliferation the latent of CTT as natural therapeutic agent for NSCLC. Therefore, we investigated the possibility of CTT as an anti-cancer agent by comparing with GF, which is a representative anti-cancer drug.
Asunto(s)
Apoptosis/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Fenantrenos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Humanos , Transducción de Señal/efectos de los fármacosRESUMEN
Araliasaponin II (AS II) is a bioactive compound isolated from Acanthopanax henryi (Oliv.) Harms, a plant widely used in traditional oriental medicine. The present study investigated the antiinflammatory effects of AS II using murine macrophages. The effects of AS II on inflammatory mediator and cytokine production in lipopolysaccharide (LPS)stimulated RAW 264.7 cells was evaluated. Nitric oxide (NO) and cytokine production were determined using the Griess reagent and an ELISA kit. The expression levels of cytokines, inducible NO synthase (iNOS) and cyclooxygenase2 (COX2) mRNA were examined by reverse transcriptionquantitative polymerase chain reaction. The expression levels of iNOS, COX2 and tolllike receptor (TLR)4 protein were examined by western blotting. Translocation of nuclear factorκB (NFκB) and TLR4 expression were visualized by immunofluorescence staining. AS II markedly inhibited the production of NO and prostaglandin E2, and reduced iNOS and COX2 expression at the transcriptional and translational levels. AS II downregulated the expression of interleukin6 and tumor necrosis factorα at the protein and mRNA levels. Furthermore, pretreatment with AS II significantly suppressed the TLR4NFκB signaling pathway; this effect may be cause by AS II competing with LPS for binding to TLR4 and subsequently inhibiting translocation of the NFκB/p65 protein to the nucleus. The results suggested that the antiinflammatory properties of AS II may result from inhibiting proinflammatory mediators by suppressing the initiation of the inflammatory response and inhibiting TLR-4-NF-κB signaling pathways.